A growing number of patients suffering from end stage renal disease are now able to survive through the use of hemodialysis and peritoneal dialysis. While hemodialysis provides life itself for these individuals, it also obligates them to a very dependent life style. Hemodialysis, generally performed at established dialysis centers, disrupts normal work schedules and severely limits travel. It may also produce a psychological burden for the patient who is time-restricted and immobilized in a center. These patients could obviously have a more pleasant, free, and productive life if treatment at home and/or office were available. The development of a portable or wearable regenerative hemodialysis system would certainly enhance the chance of home or office dialysis. Major efforts have been directed toward the development of a portable system.
Most of the proposed portable systems are based on "closed-loop" dialysis which involves regeneration of a small volume of dialysis fluid by continuously removing the dialyzed wastes. Although a large number of toxins and wastes may be removed by passage through a charcoal bed, urea, a major metabolic waste removed by dialysis, is very poorly absorbed onto charcoal. The use of one regenerative dialysis system, Sorbsystem, has demonstrated that a urea removal device and an activated charcoal bed can provide the basis for a "closed-loop" dialysis. Sorbsystem has several problems peculiar to its urea removal method: (1) the generation of toxic ammonia; (2) the instability of the enzyme, urease, used therein; (3) the limited availability of the zirconium resins used therein; and (4) the removal of essential cations which generates an ionic imbalance.
Other approaches based on the concept of electrochemical urea removal have been explored. An indirect method, Schuenemann B., Quellhorst E., Kaiser H., Richter G., Munt K., Weidlich E., Loeffler G., Zachoriae M., Schunk O. Trans Amer. Soc. Artif. Intern Organs 1982;28:49-53, electrolyzes the chloride in the dialysate to form hypochlorite and then allows the hypochlorite to chemically react with urea to form nitrogen, carbon dioxide, and water. We believe that the presence of any hypochlorite in the dialysate is unsafe for a clinical device. Hypochlorite causes hemolysis, and can react with amines to form toxic chloramines; See Ackerman RA, Coles JS. Dialysis and Transplantation 1982;11:976-977; AAMI-ASAIO Standard for hemodialysis system. 1980; (draft), Arlington, VA. At high concentration levels, hypochlorite can disrupt the cellulosic type dialysis membranes.
The earliest and simplest method for electrochemical decomposition, degradation, displacement, synthesis, etc., processes is constant current electrolysis. In this method of electrolysis, a constant magnitude of current is supplied to the electrolysis cell from a DC (direct current) power source instrument. Electrons are generated from the oxidation of chemicals at the anode where positive ions are produced. These electrons are driven or propelled by the power supply to the cathode where reduction of chemicals occurs producing negatively charged ions. The electrical circuit is then completed by the migration of the negatively charged ions toward the anode. In accordance with the principle of electroneutrality, postive ions generated from the anodic oxidation migrate toward the cathode. The amount of electricity (coulombs) consumed is simply the constant current multiplied by the time of electrolysis.
In such a constant current system, the whole cell voltage, i.e., the potential difference between the anode and the cathode, increases as the concentration of the substances being electrolyzed decreases. Different substances are electrolyzed at different potentials. Since, in this constant current electrolysis method, potential is not controlled, different electrochemical reactions may occur simultaneously. Accordingly, different substances, many undesirable, are produced. Unless a sufficiently high concentration of the desired substance is maintained, the products and the rate of electrolysis of this specific substance are unpredictable.
A more elaborate approach is controlled potential electrolysis. This method is now well-established in both analytical chemistry and industrial processes; see: H. Lund and P. Inversen, Practical Problems in Electrolysis, in Organic Electrochemistry--An Introduction and Guide, edited by M. M. Baizer, Marcel Dekker, Inc., N.Y., 1973, Chapter IV, pp. 165-249. This method of electrolysis requires three electrodes and a potentiostat. The three electrodes are the working electrode (W), the counter or auxiliary electrode (C) and the reference electrode (R). The working electrode potential, with respect to the reference electrode, is externally controlled by the potentiostat. Current is generated by a power supply in response to the oxidation or reduction of electroactive substances at W in order to satisfy the specified voltage difference (between W and R) enforced by the potentiostat. See Keller, R. W., Jr., Brown, J. M., Wolfson, S. K., Jr., Yao, S. J., "Intermittent Potential Reversal Electrolysis for Urea Removal in Hemodialysis," reported in Proceeings IEEE/1980, Frontiers of Engineering in Health Care, 1980, 2:178-181; Yao, S. J., Brown, J. M., Wolfson, S. K., Jr., Thrivikraman, K. V., Krupper, M. A., "Controlled Potential Electrolysis for Urea Removal in Hemodialysis: Improved Efficiency in Urea Clearance," reported in Proceedings of the 4th Annual Conference IEEE/1982, Frontiers of Engineering in Health Care, Philadelphia, Pa., 1982, 4:24-27.
In this controlled potential electrolysis method, current runs from W to C. Since only one of the electrode potentials, i.e., the half cell potential with respect to the reference electrode, is under control, the potential and chemical reactions at C are unpredictable. If both electrodes (W and C) are in the same reaction mixture, different species of products may be generated at C.
We have applied the controlled potential electrolysis method to direct electrochemical oxidation of urea in Krebs-Ringer buffers and in hemodialysate solution. This has been used in conjunction with development of a new regenerative hemodializer system. See Yao, S. J., Appleby, A. J., Geisel, A., Wolfson, S. K., Jr., Ahn, B. K., Liu, C. C., "Anodic Oxidation of Urea and an Electrochemical Approach to Deureation" Nature, 1973, 241:471-472. The working electrode potential was set at +0.80 V vs Ag/AgCl by means of a potentiostat. Under these conditions the potential of the counter electrode was found to be as high as -2.0 to -2.5 V vs Ag/AgCl. The whole cell voltage, i.e., the voltage difference between W and C became 2.8 V to 3.3 V. As a result of this rather large voltage difference, some undesirable or even harmful substances could be generated as reduction products at C. One needs to be very cautious about the generation of harmful products when electrolysis is applied to clinical systems.
Urea should be safely removed at a sufficient rate to be practical. The products of the electrochemical process should contain no toxic or disruptive substances. The major products of urea oxidation should be N.sub.2, CO.sub.2, and water which can be easily dissipated into the air or excreted by normal respiration.